The search for an effective strategy that would help clinicians to exclude the diagnosis of acute myocardial infarction (AMI) without the need for serial troponin testing over a number of hours has been ongoing for many years. High sensitivity troponin (hs-Tn) assays, which have greater analytical sensitivity and precision than standard assays, have been shown to improve sensitivity for AMI when measured at the time of initial presentation (1-3). However, while the negative predictive value is improved at the time of presentation, even hs-Tn cannot exclude AMI without serial sampling. Studies have also shown that hs-Tn assays can detect cardiac troponin in patients with stable heart disease who have not suffered an acute event.
As troponin is a ‘late marker’ of myocardial necrosis (blood levels may take several hours to increase significantly), there has been significant interest in using so-called ‘early markers’ of myocardial necrosis to exclude AMI during the period of ‘troponin blindness’. The most extensively investigated strategy involves ‘triple marker testing’ for troponin, creatine kinase MB fraction (CK-MB) and myoglobin (4). A recent multinational study suggested that this strategy may help to exclude AMI in less than 10% of patients, even with serial sampling over 2 hours (5). The strategy relies on selection of a very low risk patient group through clinical risk scoring as the biomarker panel has a sensitivity of only 82.1%. Additional work has demonstrated that this strategy is not cost-effective (6, 7).
Heart fatty acid binding protein (H-FABP) is contained within the cytoplasm of cardiac myocytes and has shown promise as an alternative ‘early marker’ of AMI. Compared to standard troponin assays, H-FABP has superior sensitivity for AMI in patients who present early (<4 h) after symptom onset (8). H-FABP and troponin (using standard assays) are independent predictors of prognosis (9). It has previously been demonstrated that the combination of troponin (using a standard assay) and H-FABP is unequivocally superior to triple marker testing for early diagnosis at the time of presentation to the ED (10). However, it is not known whether H-FABP adds incremental diagnostic value when high sensitivity troponin assays are used.
The electrocardiograph (ECG) is a commonly used diagnostic tool in cases of suspected myocardial infarction. It records the rhythm and electrical activity of the heart and can indicate abnormalities. However the ECG can appear normal in cases of ischemia or infarction and therefore in isolation it cannot rule out AMI.
There remains a clinical need for a strategy to better enable diagnosis when a patient presents with chest pain. A quick and accurate diagnosis means patients requiring treatment can be administered to immediately and those who don't can be reassured and released. As described herein the current invention enables a method to improve diagnosis of AMI and help predict future risk of a major adverse cardiac event (MACE).